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image of Comparative in Vitro Metabolic Profile Study of Five Cathinone Derivatives

Abstract

Background

Cathinone derivatives as new psychoactive substances have attracted worldwide attention in recent years. They have strong excitatory effects on the human central nervous system, which is extremely abusive and harmful. As they are easy to be structurally modified, and rapidly metabolized and excreted after taken, clarifying their metabolic profile is of significant importance to provide useful information for their identification or forensic purposes.

Objective

In this paper, a comparative metabolic profile study of five cathinone derivatives (4/3/2-methylmethcathinone and 4/3-methoxymethcathinone) was performed, including their metabolic stability in the simulated gastrointestinal tract, mass spectrometry fragmentation behavior, possible metabolic pathways and metabolites in human liver microsomal incubation system, and revealing the key metabolic enzyme isoforms involving in their biotransformation.

Methods

incubation was performed in simulated gastric/intestinal fluid and human liver microsomes, fragmentation behavior study and metabolite identification were investigated by LC-Q-TOF/MS, and metabolic stability study, along with metabolic enzyme screening were analyzed using LC-MS/MS.

Results

Almost all the cathinone derivatives tested were stable in the simulated gastric/intestinal fluid; characteristic fragmentation pathway and diagnostic fragment ions of the cathinone derivatives were analyzed; the key metabolic pathways of 4/3-methylmethcathinone and 4/3-methoxymethcathinone revealed were hydroxylation and demethylation, which were catalyzed by CYP2D6. The methyl-substituted position would significantly affect the metabolic pathway of the methylmethcathinone.

Conclusion

This study revealed the mass spectral fragmentation pattern and the metabolic behavior of the selected cathinone derivatives, providing meaningful information and scientific evidence in predicting their metabolic potential , and also promoting their analysis, detection, and clinical use.

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2025-03-17
2025-05-13

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Comparative in Vitro Metabolic Profile Study of Five Cathinone Derivatives
Bentham Science Publishers ; https://doi.org/10.2174/0113892002348484250309011657
/content/journals/cdm/10.2174/0113892002348484250309011657
/content/journals/cdm/10.2174/0113892002348484250309011657
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  • Article Type:     Research Article
Keywords: metabolism study ; metabolic enzyme ; human liver microsomes ; metabolic behavior ; LC-Q-TOF/MS ; Cathinone derivatives

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